A variety of medical disorders result from impaired functions of specific cells. For example, type I diabetes is an autoimmune disorder arising from destruction of insulin-producing beta-cells of the pancreas. The beta-cells are part of the islets of Langerhans (“islets”). The islets contain five types of endocrine cells, including beta-cells. Therapy for type I diabetes typically involves insulin injections, where this therapeutic approach had an origin in the isolation, by Banting and Best, of an “active principle” from whole pancreas (Rosenfeld (2002) Clin. Chem. 48:2270-2288; Best (1945) Can. Med. Assoc. J. 53:204-212). A continuing risk with insulin injections, for example, is the adverse event of hypoglycemia arising from an insulin overdose (Jamiolkowski et al (2012) Yale J. Biol. Med. 85:37-43).
Another approach for treating type I diabetes, as well as other disorders arising from deficiencies in specific cells, is cell transplantation. Cell transplantation can involve autologous transplantation, where the host's own cells are harvested, then cultured or modified ex vivo, and then reintroduced into the host. Cell transplantation can also involve allogeneic transplantation, where cells from another human host, genetically related or genetically non-related, are harvested from the other human host and then implanted into the recipient human host. Yet another approach is xenotransplantation, where cells derived from another species are transplanted into a human.
Allogeneic transplantation and xenogenic transplantation result in the adverse event of the host's immune response against the transplanted cells. To mitigate this adverse event, researchers have encapsulated cells prior to transplanatation. Encapsulation has been with a natural polymer such as alginate, or with synthetic polymers, such as hydroxyethyl methacrylate-methyl methacrylate or polyethylene glycol (PEG). Another approach has been to encapsulate cells in a small device, for example, a device made of polysilicon, alumina, or epoxy-based polymers. The term “implant,” in this context, generally refers to mammalian cells that have a coating, or that are contained in a device, and where the coated cells or where the device is implanted in a human host.
Regarding the transplantation of coated cells, problems include the deterioration of the coating over a period of weeks or months, failure of cells to thrive due to inadequate supply of oxygen, growth of fibroblasts over the implant, and the host's immune response against the cells (see, e.g., Vaithilingam and Tuch (2011) Rev. Diabetic Studies. 8:51-67). Some of the above problems result from a pore size that is too large, and that allows the host's antibodies to enter the capsule. Immune response against the cells can be exacerbated by the coating itself, for example, where the coating includes polyornithine. Yet another problem, also related to the nature of the polymers, is where polymers are crosslinked over the cells, and where crosslinking is by way of toxic free radicals. Moreover, another problem with encapsulation technology are attempts to manufacture overly complex capsules, such as those using several different layers (see, e.g., Wang et al (2008) Transplantation. 85:331-337).